SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer

Pengchao Sun,* Nan Zhang,* Yafang Tang, Yanan Yang, Xiao Chu, Yongxing Zhao Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan, People’s Republic of China *These authors contributed equally to the work Abstract: DNA nanostructures prep...

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Autores principales: Sun P, Zhang N, Tang Y, Yang Y, Chu X, Zhao Y
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:df2d11038dd44802a73c8137ece88f242021-12-02T01:01:50ZSL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer1178-2013https://doaj.org/article/df2d11038dd44802a73c8137ece88f242017-04-01T00:00:00Zhttps://www.dovepress.com/sl2b-aptamer-and-folic-acid-dual-targeting-dna-nanostructures-for-syne-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Pengchao Sun,* Nan Zhang,* Yafang Tang, Yanan Yang, Xiao Chu, Yongxing Zhao Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan, People’s Republic of China *These authors contributed equally to the work Abstract: DNA nanostructures prepared by self-assembly possess good stability, high biocompatibility, and low immunogenicity as drug delivery vehicles. In this work, DNA tetrahedron (TD) was constructed and modified with SL2B aptamer (S) and folic acid (F). TD possessed a small diameter (~6 nm) and entered into the nucleus quickly. SL2B aptamer can inhibit cancer cell growth by disturbing vascular endothelial growth factor/Notch signaling pathways. To explore the effect of SL2B number on colorectal cancer inhibition, SL2B multimers (dimer, trimer, and tetramer) were constructed by functionalization of TD with different numbers of SL2B. One SL2B per TD was the most efficient anticancer strategy and showed significantly better anticancer efficacy than SL2B, probably due to the enhanced stability of SL2B by TD. Doxorubicin (DOX) is a potent anticancer agent that can intercalate into DNA double strands. Results showed that TD could facilitate DOX entrance into the nucleus and the intracellular delivery of DOX was further enhanced by functionalization of SL2B and F. DOX-intercalated TD modified with two F and two S (DOX@TD-2F2S) could cause sufficient HT-29 cell inhibition at a much lower DOX concentration. In sum, DOX@TD-2F2S exhibited a synergic anticancer biological effect with chemotherapy and can be a promising strategy for treating colorectal cancer. Keywords: SL2B aptamer, DNA tetrahedron, synergic biological effect with chemotherapy, colorectal cancer, doxorubicin, VEGF/Notch, folic acidSun PZhang NTang YYang YChu XZhao YDove Medical PressarticleDNA tetrahedronSL2B aptamerDoxorubicincolorectal cancercombined biological and chemotherapyVEGF/Notch signaling pathwayMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2657-2672 (2017)
institution DOAJ
collection DOAJ
language EN
topic DNA tetrahedron
SL2B aptamer
Doxorubicin
colorectal cancer
combined biological and chemotherapy
VEGF/Notch signaling pathway
Medicine (General)
R5-920
spellingShingle DNA tetrahedron
SL2B aptamer
Doxorubicin
colorectal cancer
combined biological and chemotherapy
VEGF/Notch signaling pathway
Medicine (General)
R5-920
Sun P
Zhang N
Tang Y
Yang Y
Chu X
Zhao Y
SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
description Pengchao Sun,* Nan Zhang,* Yafang Tang, Yanan Yang, Xiao Chu, Yongxing Zhao Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan, People’s Republic of China *These authors contributed equally to the work Abstract: DNA nanostructures prepared by self-assembly possess good stability, high biocompatibility, and low immunogenicity as drug delivery vehicles. In this work, DNA tetrahedron (TD) was constructed and modified with SL2B aptamer (S) and folic acid (F). TD possessed a small diameter (~6 nm) and entered into the nucleus quickly. SL2B aptamer can inhibit cancer cell growth by disturbing vascular endothelial growth factor/Notch signaling pathways. To explore the effect of SL2B number on colorectal cancer inhibition, SL2B multimers (dimer, trimer, and tetramer) were constructed by functionalization of TD with different numbers of SL2B. One SL2B per TD was the most efficient anticancer strategy and showed significantly better anticancer efficacy than SL2B, probably due to the enhanced stability of SL2B by TD. Doxorubicin (DOX) is a potent anticancer agent that can intercalate into DNA double strands. Results showed that TD could facilitate DOX entrance into the nucleus and the intracellular delivery of DOX was further enhanced by functionalization of SL2B and F. DOX-intercalated TD modified with two F and two S (DOX@TD-2F2S) could cause sufficient HT-29 cell inhibition at a much lower DOX concentration. In sum, DOX@TD-2F2S exhibited a synergic anticancer biological effect with chemotherapy and can be a promising strategy for treating colorectal cancer. Keywords: SL2B aptamer, DNA tetrahedron, synergic biological effect with chemotherapy, colorectal cancer, doxorubicin, VEGF/Notch, folic acid
format article
author Sun P
Zhang N
Tang Y
Yang Y
Chu X
Zhao Y
author_facet Sun P
Zhang N
Tang Y
Yang Y
Chu X
Zhao Y
author_sort Sun P
title SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
title_short SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
title_full SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
title_fullStr SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
title_full_unstemmed SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
title_sort sl2b aptamer and folic acid dual-targeting dna nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/df2d11038dd44802a73c8137ece88f24
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